title: Antioxidant supplementation and premature rupture of the membranes: a planned secondary analysis.
abstract: OBJECTIVE
  The purpose of this study was to determine if antioxidant supplementation during pregnancy reduces the incidence of premature rupture of the membranes (PROM).
  
  
  METHODS
  A placebo-controlled, double-blind trial was conducted. PROM and preterm PROM (PPROM) were planned secondary outcomes of the trial. Women between 12(0/7) and 19(6/7) weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomized to daily treatment with both vitamin C (1000 mg) and E (400 IU) or placebo.
  
  
  RESULTS
  Outcome data for PROM were available for 697 of 739 patients. The rates of PROM (37/349 [10.6%] vs 19/348 [5.5%]; adjusted risk ratio [RR] 1.89 [95.42% CI, 1.11-3.23]; P = .015), and PPROM (16/349 [4.6%] vs 6/348 [1.7%]; RR 2.68 [1.07-6.71]; P = .025) were increased in the antioxidant group.
  
  
  CONCLUSIONS
  Contrary to expectations, vitamins C and E supplementation in this dose combination may be associated with an increased risk of PROM and PPROM.
authors.affiliation: University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Spinnato
authors.forename: Salvio
authors.initials: S
authors.lastname: Freire
authors.forename: Joao Luiz
authors.initials: JL
authors.lastname: Pinto e Silva
authors.forename: Marilza Vieira Cunha
authors.initials: MV
authors.lastname: Rudge
authors.forename: Sérgio
authors.initials: S
authors.lastname: Martins-Costa
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Koch
authors.forename: Norman
authors.initials: N
authors.lastname: Goco
authors.forename: Cleide de Barros
authors.initials: Cde B
authors.lastname: Santos
authors.forename: Jose Guilherme
authors.initials: JG
authors.lastname: Cecatti
authors.forename: Roberto
authors.initials: R
authors.lastname: Costa
authors.forename: José Geraldo
authors.initials: JG
authors.lastname: Ramos
authors.forename: Nancy
authors.initials: N
authors.lastname: Moss
authors.forename: Baha M
authors.initials: BM
authors.lastname: Sibai
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage*; D019587:Dietary Supplements; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D011247:Pregnancy; D011256:Pregnancy Outcome; D011446:Prospective Studies; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D014810:Vitamin E; D001205:Ascorbic Acid